RT-QuIC Testing for Prions: Applying a Sensitive but Imperfect Test in Clinical Practice (P5-12.010)

Abstract

<h3>Objective:</h3> Identify the clinical, laboratory, and pathologic features associated with false negative real-time quaking-induced conversion (RT-QuIC) testing for prions. <h3>Background:</h3> Heterogeneity in clinical presentation, abundant mimics, and potential for iatrogenic transmission emphasize the need for accurate diagnostic tests for Creutzfeldt-Jakob disease (CJD). While RT-QuIC is an excellent test, false negative results are recognized in clinical practice. <h3>Design/Methods:</h3> One-hundred twelve patients with probable or definite prion disease were assessed at two tertiary care centers from 2013–2021. RT-QuIC testing for prions was performed in cerebrospinal fluid (CSF) in all patients via the National Prion Disease Pathology Surveillance Center (Cleveland, OH). Demographic data, clinical features, and results of common tests and laboratory studies were abstracted from electronic medical records, and differences between RT-QuIC positive and negative patients considered using univariate statistics. <h3>Results:</h3> Initial RT-QuIC testing was negative in 12/112 patients (sensitivity 89%). Median age at presentation was younger in RT-QuIC negative patients (56.9 vs 66 years, p&lt;0.01), who were also less likely to present with ataxia (3/12 vs 61/100, p=0.03). CSF cell count, protein, and glucose levels were similar between cohorts, while rates of 14-3-3 positivity (2/12 vs 77/100, p&lt;0.01) and median CSF total tau levels were lower in RT-QuIC negative patients (2318 vs 4001 pg/mL, p&lt;0.01). RT-QuIC negative patients also had a longer median days from symptom onset to first presentation (125 vs 47, p=0.04), and longer symptomatic disease duration (530 vs 148, p&lt;0.01). Two RT-QuIC-negative patients underwent repeat testing, of which both were positive. <h3>Conclusions:</h3> RT-QuIC is a sensitive yet imperfect measure necessitating incorporation of other test results when prion disease is suspected. Patients with negative RT-QuIC had lower CSF biomarkers of neuronal damage (total-tau and 14-3-3) and longer symptomatic duration of prion disease raising the possibility that false negative RT-QuIC testing may associate with a more indolent disease course. <b>Disclosure:</b> Dr. Jones has nothing to disclose. Dr. Lazar has nothing to disclose. Dr. Porter has nothing to disclose. Dr. Prusinski has nothing to disclose. Dr. Brier has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. The institution of Dr. Brier has received research support from NIH. Dr. Bucelli has received personal compensation for serving as an employee of Biogen. Dr. Bucelli has received personal compensation for serving as an employee of Biogen. Dr. Bucelli has received personal compensation for serving as an employee of Neuroquestions. Dr. Bucelli has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen . Dr. Bucelli has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Bucelli has stock in Neuroquestions.com. An immediate family member of Dr. Bucelli has stock in Neuroquestions.com. The institution of Dr. Bucelli has received research support from Biogen. The institution of Dr. Bucelli has received research support from Ionis. Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Parabon Nanolabs. The institution of Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Eli Lilly. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for DynaMed (EBSCO Health). Dr. Day has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Barrow Law. Dr. Day has stock in ANI Pharmaceuticals. The institution of Dr. Day has received research support from National Institutes of Health / NIA. The institution of Dr. Day has received research support from Chan Zuckerberg Initiative. The institution of Dr. Day has received research support from Alzheimer’s Association. The institution of Dr. Day has received research support from National Institutes of Health / NINDS. The institution of Dr. Day has received research support from Horizon Therapeutics. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as a Presenter at Annual Meeting (CME) with American Academy of Neurology. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as a Content Development (CME) with PeerView, Inc. Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving as a Content Development (CME) with Continuing Education, Inc. Dr. Day has a non-compensated relationship as a Clinical Director with AntiNMDA Receptor Encephalitis Foundation that is relevant to AAN interests or activities.